Method for preparing isocyanates from halosilyl carbamates

ABSTRACT

Isocyanates are prepared directly from amines in a facile process which involves the reaction with halosilyl compounds to form novel halosilyl carbamates. The isocyanate may then be derived from the carbamate intermediate by gentle heating. In accordance with one aspect of the invention, isocyanates can be formed which contain a further reactive functional moiety, such as hydroxyl, amino, mercapto, nitro, sulfonamido, amido, carboxyl or the like.

This is a division of our prior U.S. application Ser. No. 678,160 filedMay 17, 1976 and now U.S. Pat. No. 4,064,151.

RELATED APPLICATION

Hedaya, Eisenhardt and Theodoropulos, for: Analytical or ClinicalDerivatives, Tagged Derivatives and Methods of Analysis Using SuchDerivatives, application Ser. No. 687,149, filed May 17, 1976.

BACKGROUND OF THE INVENTION

This invention relates to isocyanates and, more particularly, to amethod for synthesizing isocyanates utilizing novel halosilyl carbamatesand to the novel halosilyl carbamates.

While other techniques are known, the commercial manufacture ofisocyanates is carried out almost exclusively by the reaction of amineswith phosgene. The details of processing may vary somewhat with thespecific isocyanate being formed, and in particular for aromatic andaliphatic isocyanates, but the general approach is the same. The use ofphosgene is undesirable due to its toxicity as well as the care whichmust be utilized when employing it. In addition, the reaction conditionswhich are required restrict, to some extent, the type of isocyanateswhich may be prepared. The problems are multiplied in the manufacture ofa diisocyanate, where the simple by-products may be intermolecular, e.g.-- a mixed carbamyl chloride/amine hydrochloride, and the ureaby-products may be polymeric.

Various silicon derivatives have been employed previously to provideintermediates which break down to yield isocyanates. In Russian ChemicalReviews, Vol. 42, p. 669, (1973), a decomposition of an N-silylatedcarbamic ester under heating to provide isocyanates is disclosed:##STR1## A dehydrative pyrolysis of a silyl carbamate is described inthe translation of the Russian Journal of General Chemistry, Vol. 43, p.2077 (1973), UDC 547,245: ##STR2## Still further, Angewandte Chemie,Vol. 70, p. 404 (1958), shows the formation of a highly substitutedisocyanate from N-carbobenzoxy amino acid using trimethylsilyl chloride:##STR3## In addition, in Angewandte Chemie, International Edition of1968, at page 941, Vol. 7, there is described the thermal decompositionof nitrogen-substituted trimethylsilylated derivatives of carbamic acidesters, anhydrides, or chlorides. The reaction is shown below, Yreferring to the acid derivatives previously mentioned: ##STR4##

None of the prior work shows the direct, continuous, synthesis of anisocyanate from an amine without the use of phosgene. Still further, ingeneral, the reactions also require a relatively high forcing level ofheating to yield the isocyanate.

It is accordingly an object of the present invention to provide adirect, continuous method for preparing isocyanates from amines withoutemploying phosgene.

A further object provides a continuous method for the synthesis ofisocyanates from amines which include other reactive, functional groups.A related and more specific object is to provide a method of preparingisocyanates from amines which also include hydroxyl, amino, mercapto,nitro, sulfonamido, amido or carboxylic groups.

Yet another object lies in the provision of preparing halosilylcarbamates.

Another object of this invention is to provide a method of preparingisocyanates in which the isocyanates are synthesized by heatingintermediates under mild conditions.

A further object provides a method of preparing isocyanates which can becarried out in a single reaction vessel.

Other objects and advantages of the present invention will becomeapparent from the following detailed description.

While the invention is susceptible to various modifications andalternative forms, there will herein be described in detail thepreferred embodiments. It is to be understood, however, that it is notintended to limit the invention to the specific forms disclosed. On thecontrary, it is intended to cover all modifications and alternativeforms falling within the spirit and scope of the invention as expressedin the appended claims.

SUMMARY OF THE INVENTION

In general, the present invention is predicated on the discovery thatisocyanates may be directly synthesized from amines by forming novelisocyanate intermediates, namely, halosilyl carbamates. In accordancewith one procedure, the primary amine utilized is converted to itscarbamic acid salt which is then reacted with a silane preferablycontaining at least two halogen atoms bonded to the silicon to form thehalosilyl carbamate. The isocyanate is then formed from the carbamate,by gentle heating. In accordance with an alternative procedure,isocyanates may be formed which can contain a reactive functional groupin addition to the isocyanato group. Such reactive functional groups areblocked in the synthesis to prevent polymerization, internal cyclizationor the like which might typically otherwise occur. To this end, thecarbamic acid salt is first converted to its silylcarbamate which isthen converted to the halosilyl carbamate by employing a noveltrans-silylation reaction.

The resulting isocyanates may be used for any of the several utilitieswhich are well-known for this type of compound. For example, isocyanatesare widely used for forming foams, elastomers and coatings as well as,principally in the case of monofunctional compounds, for themodification of organic compounds. Non-polymer applications forisocyanates lie largely in the field of insecticides, herbicides, andother biologically active products.

DETAILED DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS

In accordance with the method of the present invention, a primary amineis first reacted with carbon dioxide to form the carbamic acid salt:

    2 RNH.sub.2 + CO.sub.2 → RNHCOO.sup.- N.sup.+ H.sub.3 R

this reaction is well-known and is described in the followingliterature: Fichter and Becker, Ber., Vol. 44, p. 3041 (1911); Frankel,Neufeld and Katchalski, Nature, Vol. 144, p. 832 (1939); Frankel andKatchalski, J. Amer. Chem. Soc., Vol. 65, p. 1670 (1943); Wright andMoore, J. Amer. Chem. Soc., Vol. 70, p. 3865 (1948) and Hayashi, Bull.Inst. Phys. Chem. Vol. 11, p. 133 (1932).

Functionally, R can be defined, as is known, as any moiety which as anamine is strong enough as a base to form a carbamate salt with the weakacid, carbon dioxide. Thus, alkyl groups such as methyl, ethyl, butyl,octyl and the like may be employed. Cycloalkyl and halosubstituted alkylgroups may likewise be utilized. In addition, cycloalkyl andhalosubstituted cycloalkyl groups such as cyclohexyl, cyclopentyl,3-chloropropyl and 4-bromocylohexyl groups are useful. Still further,aralkyl groups such as benzyl will also form a carbamate and are withinthe scope of the present invention.

Other useful groups include alkyl ethers, cyclic ethers such as furanand pyran, thioethers such as thiophenes, cyclic amines such as pyridineand pyrrols, imadazoles, oxazoles, thiazoles, sulfonamides, glycosides,sugars and other carbohydrates and chitin/chitosan.

Still further, aryl and alkaryl groups such as phenyl, tolyl, xylyl andnaphthyl may not form carbamates by reaction as an amine; but theiramine salts such as lithium anilide, potassium naphthylamine, sodiumanthrayl amine and the like may be used since the salts are strongerbases than the parent amine.

The cited literature also discloses useful amines which may be utilizedif desired. The disclosure of such literature is incorporated byreference.

It should be further appreciated that the amine reactant selected can bepolyfunctional. Thus, diamines, triamines and the like may be employedwhere polyfunctional isocyanates are desired. Alternatively, whenpolyfunctional amines are used, one or more of the amino groups can, ifdesired, be blocked by any of the known techniques in such a fashion asto survive the formation of the isocyanate. After isocyanate formation,the blocked group or groups may then be suitably deblocked, as is known.

A solvent may be employed for the amine to control the temperature andto moderate the rate of reaction; however, if the starting amine is aliquid, a solvent is not absolutely necessary. Either a polar or anonpolar solvent may be employed. Useful polar solvents include tertiaryamines such as, for example, triethylamine. Representative examples ofnonpolar solvents include hydrocarbons, halogenated hydrocarbons,ethers, and nitriles. Suitable specific examples include hexane,toluene, tetrahydrofuran and acetonitrile. Solvents containing reactivegroups, such as alcohols, are not desirably employed because suchsolvents would interfere with the reaction.

If a tertiary amine is used as a solvent, this will enter into thereaction. This sequence is shown below with triethylamine:

    RNH.sub.2 + CO.sub.2 .sup.(C.sbsp.2.sup.H.sbsp.5.sup.).sbsp.3.sup.N RNHCOO .sup.- N.sup.+ H(C.sub.2 H.sub.5).sub.3

the useful process parameters, as is known in the literature, may varyover a wide range. Stoichiometric amounts will generally be preferred,as deficiencies reduce yields. The use of an excess does not apparantlycause any adverse effects. If employed, the amount of solvent used willgenerally be dependent upon the reason for utilization. Thus, forexample, if a solvent is used for moderating the rate of reaction, theamount of solvent employed will be determined by the extent ofmoderation desired.

The temperature of the reaction may be carried out over a wide range,varying from about ambient temperatures to about 150° C. However, it ispreferred to use lower temperatures in the range of from about 30° to60° C. to minimize the formation of any side products.

While the reaction has been described in connection with carbon dioxide,it should be appreciated that carbon disulfide or carbon oxysulfide mayalso be suitably employed. In such cases, isothiocyanates willultimately be formed. Conceptually, more than one of such compoundscould be employed. Also, when a polyamine such as a diamine is utilized,it might be desired to use both carbon dioxide and carbon disulfide. Inthis fashion, the ultimate product could possess thioisocyanato as wellas isocyanato groups. To achieve this type of product, due to differingreactivities, it will generally be desired to initially react the aminewith carbon disulfide and then to react the resulting intermediate withcarbon dioxide.

As will be appreciated, when either carbon oxysulfide or carbon dioxideare utilized, the criteria for useful amines is the same as has beendiscussed in connection with carbon dioxide. Thus, any amine may be usedif it or its amine salt is strong enough to form the corresponding saltwith the oxysulfide or disulfide.

The second step of the procedure involves formation of the novelhalosilyl carbamate by reacting the carbamic acid salt with a silanecontaining at least two halogen atoms bonded to the silicon. Thisreaction sequence is set forth below:

    RNHCOO .sup.- N.sup.+ H.sub.3 R + SiY.sub.2 X.sub.2 → RNHCOOSiXY.sub.2

in the reaction, X defines a halogen atom and may suitably be fluorine,chlorine, bromine or iodine. Y defines either a halogen, hydrogen or anorganoic moiety. Conceptually, any organic moiety which allows formationof a halosilyl carbamate and the subsequent conversion to thecorresponding isocyanate, as will be described hereinafter, may besuitably utilized. With stoichiometric amounts, the halosilyl carbamatesare formed in a substantially quantitative yield. Representative usefulorganic moieties include lower alkyls containing up to about 10 carbonatoms such as dimethyl, methyl ethyl or methyl propyl. Alicyclic groupssuch as cyclopentyl, cyclohexyl or cycloheptyl may also be utilized butshould contain about 10 carbon atoms or less. Still further, aryl andalkaryl groups containing up to about 10 carbon atoms may be used.Suitable examples include phenyl, tolyl and xylyl. In addition, aralkylgroups containing up to about 10 carbon atoms such as benzyl may also beused. Any of these moieties may be substituted with one or more halogenatoms. It should be understood that the utilization of organic moietieshaving about 10 carbons or less represents a preference rather than alimitation. Availability and cost will often dictate the particularsilane utilized. A further consideration is the ease of conversion tothe isocyanate, larger and bulkier organic molecules generally providinga less facile conversion.

It is believed that one halogen atom of the silylating agent serves asan amine acceptor to neutralize the amine from the positive radical ofthe carbamic acid salt while, of course, the other halogen atom isretained in the reaction product. It is preferred to utilize asilylating agent containing more than two halogen atoms inasmuch as itis believed that the more electron-withdrawing halogen atoms bonded tothe silicon, the more facile will be the formation of the desiredisocyanate. It is thus preferred to employ tetrachlorosilane.Phenyltrichlorosilane and dimethyldichlorosilane are furtherrepresentative examples of useful species.

In addition, while chlorosilanes will be typically preferred due totheir more ready availability and economy, other electronegative atomsor moieties such as carboethoxy, ethoxy and acetyl groups might likewisebe utilized.

The formation of the halosilyl carbamates may suitably be carried out inthe same reaction vessel that was utilized in forming the carbamic acidsalt; and, indeed, these steps may be carried out simultaneously. Theprocess parameters employed may thus be the same as described herein inconnection with the initial step of the reaction.

The resulting halosilyl carbamate, once formed, will slowly generate theisocyanate correponding to the original primary amine. When the reactionmixture is heated, the isocyanate can be distilled from the siliciouspolymer formed, as shown in the reaction sequence below:

    RNHCOOSiCl.sub.3 .sup.heat RN═C═O

the temperature range utilized for the conversion to the isocyanate mayvary widely and will typically range from about ambient to about 150° C.The isocyanate may be recovered by conventional means in yieldsapproaching a quantitative level. Recovery of isocyanates in yields of80 to 90 percent or even more can generally be achieved. It isunnecessary to isolate the halosilyl carbamate as part of the method;however, if desired, this can be accomplished. The isolated product maybe characterized by infrared or nuclear magnetic resonance spectroscopy.While primarily useful in the context of this invention as intermediatesin the preparation of isocyanates, the halosilyl carbamates may beutilized in purification of chemical compounds, being used in the samemanner as other known silylating agents to, for example, increase thevolatility and alter the polarity of the compound being purified.

As can be seen, the halosilyl carbamate contains two oxygen atoms, oneof which may be termed the carbonyl oxygen and the other, the esteroxygen. It is believed that this intermediate forms the isocyanate bycleavage of the carbonester oxygen bond of the carbamate withconcomitant removal of the hydrogen atom from the nitrogen. It isbelieved that the electronegative character of the chlorine or otherhalogen atoms bonded to the silicon atom facilitates this cleavage.

In the alternative procedure, which may be termed the exchangeprocedure, the carbamic acid salt formed in the first step of the priorprocedure described herein is treated with any halosiliane to form thesilylcarbamate. This is illustrated below in the instance whereintriethylamine was used as a solvent:

    RNHCOO.sup.- HN.sup.+ (C.sub.2 H.sub.5).sub.3 + R'.sub.3 SiX → RNHCOOSiR'.sub.3

alternatively, the silylcarbamate could be prepared by insertion of thecarbon dioxide by means other than utilizing the carbamic acid salt. Inany case, in contrast to the carbamic acid salts which are hygroscopicand may sometimes revert to the amine with the loss of carbon dioxide,the silylcarbamates are generally water-white liquids which can bepurified, if desired.

In accordance, with one aspect of the present invention, thesilylcarbamate is subjected to a novel trans-silylation reaction toconvert the silylcarbamate to a halosilyl carbamate. This reaction isset forth below:

    RNHCOOSiR'.sub.3 + SiY.sub.2 X.sub.2 → RNHCOOSiY.sub.2 X

with regard to the reactants, R' of the halosilane represents an organicmoiety which may be any of the moieties previously described inconnection with the halosilane utilized in the first procedure.Similarly, the halosilane utilized in the trans-silylation reaction maybe of the compounds identified in connection with the halosilanes usefulin the first procedure.

The haloslyl carbamate, as was described in connection with the initialprocedure, will slowly generate the corresponding isocyanate. This maybe separated from the exchange reaction mixture by distillation or byfiltration, if desired. Silicious polymers will remain in the residue.

The various solvents utilized in the initial procedure as well as thetemperature ranges may be also used for the exchange procedure. In theinitial procedure, the reaction times will typically vary from aboutfive minutes to about two hours, depending upon the temperatures used,the number and size of substituent groups in the reactants, and thehalogen atoms involved. Most typically, the reaction times will fall inthe range of from about 15 to about 45 minutes. In the exchangeprocedure, the reaction times will typically be longer, ranging fromabout one hour to about six hours.

In both procedures, exact stoichiometric amounts of the reagents areunnecessary, but yields of isocyanates will not be detrimentallyaffected by employing a slight excess of the silylating agents. Purityof the reactants employed is not critical, except, however, all of thereactants should be dried since water interferes by reacting with boththe halogen-containing silylating reactants and with the isocyanateproduct. Sufficient drying may be achieved by drying the reactants overmolecular sieves.

The essential difference between the two procedures resides in theformation of a blocked halosilyl carbamate in the exchange procedure aswell as the requirement, in that procedure, of the use of two silylatingreagents. Thus, in accordance with one aspect of the present invention,the exchange procedure, which may be carried out in one vessel in aseries of steps, can be advantageously employed in situations where theamine contains reactive functionality such as, for example, hydroxyl orcarboxyl. The blocked group survives the formation of the isocyanate andmay then be suitably deblocked by known techniques when desired. Inaddition, if desired, the silylcarbamate intermediate may be purified,as by distillation or recrystallization, for applications where aparticularly pure isocyanate is desired.

The normal procedure (the initial procedure described), which also maybe carried out in one reaction vessel, may prove mor economical due tothe fewer reagents and steps needed. Thus, this procedure may be moresuitable for synthesizing isocyanates when relatively large quantitiesare needed.

It should also be appreciated that, while the processes of the presentinvention have been described in conjunction with silicon reactants,similar reagents of other elements in Group IV or V could likewise beutilized. As representative examples, compounds of tin and germaniumcould be used. In addition, it is believed that compounds of sulfur,titanium and phosphorus would be useful.

The following Examples are illustrative, but not in limitation, of thepresent invention.

As used in the Examples appearing hereinafter, the followingdesignations symbols, terms and abbreviations have the indicatedmeanings:

mol: mole

ml: milliliter

bp: boiling point

g: gram

Thf: tetrahydrofuran

ppm: parts per million

m: multiplet

t: triplet

d: doublet

s: singlet

q: quartet

J: coupling constant

eV: electron volts

R_(f) : In thin layer chromatography, the proportion of length of climbof a solution that is reached by a spot characteristic of one of theconstituents present.

Hz: Hertz

ir: infrared

nmr: nuclear magnetic resonance

EXAMPLE 1

Two independent experiments were run synthesizing methyl isocyanate, oneutilizing chlorobenzene (bp 132° C.) as the solvent, the other usingmixed xylenes (bp 139°-144° C.) as the solvent. A 500 ml, three-neckedflask was fitted with a Dry Ice/acetone-cooled condenser. About 50g ofDry Ice pieces were placed in the flask and then about 50g of gaseousmethylamine was passed in, thus quantitatively forming methylammoniummethylcarbamate. After removal of the cooling condenser, the excess DryIce was allowed to sublime.

In separate experiments, 21g (0.2 mol) of the carbamic acid salt and 100ml of each of the above dry solvents were stirred magnetically at roomtemperature for 30 minutes after 24 ml (0.2 mol) of silicontetrachloride had been added to the flask which was previously fittedwith a distillation column and thermometer. The reaction vessel was thenheated over a 30 minute period to 100°-120° C.

In this temperature range, the methyl isocyanate (bp 42° C.) distilledoff as rapidly as it was formed. The fraction distilling at 40°-48° C.was in each case separately redistilled resulting in 9g of product ineach experiment, a yield of 80%.

EXAMPLES 2-4

The same procedure employed in Example 1 was repeated three times withpropylamine substituted for methylamine, using different solvents andstoichiometries. Propyl isocyanate (bp 80°-82° C.) was produced asfollows:

    ______________________________________                                                            Molar Ratio                                               Example Solvent     SiCl.sub.4 /Carbamate                                                                        % Yield                                    ______________________________________                                         2a     p-xylene    1              98                                         3       bis-2-methoxy                                                                             1              70                                                 ether                                                                 4       bis-2-methoxy                                                                             0.5            59                                                 ether                                                                 ______________________________________                                    

EXAMPLE 5

Into a 500 ml, three-necked flask fitted with reflux condenser, gasinlet tube, and magnetic stirrer, under a nitrogen atmosphere wascharged 19.8g (0.2 mol) of cyclohexylamine. Carbon dioxide from a gascylinder was allowed to pass in for five minutes to form,quantitatively, 24.2g (0.1 mol) of cyclohexylammoniumcyclohexylcarbamate. 150 ml of tetrahydrofuran (THF) dried over 1/16inch activated molecular sieves and 12.0 ml (0.1 mol) of silicontetrachloride were then charged into the flask, and the reaction mixturewas allowed to stir overnight at room temperature under nitrogen.

The trichlorosilyl carbamate in solution was then separated from theprecipitated amine hydrochloride solid by filtration, using a sinteredglass funnel. After washing the filter cake with 20 ml of dry THF, thefiltrate and washings were concentrated with a rotary evaporator at30°-40° C. under about 12 torr pressure for about 15 minutes.

The concentrate trichlorosilyl carbamate was decomposed for about 10minutes at 130°-150° C. at about 12 torr and then distilled.Redistillation gave 12.2g of cyclohexyl isocyanate bp 167°-169° C. (98%yield).

EXAMPLE 6

This Example illustrates the use of triethylamine as a neutralizingreagent for the by-product hydrogen chloride formed.

Into a flask fitted with a reflux condenser, gas inlet tube, andmagnetic stirrer, under a nitrogen atmosphere, was charged 50 ml of drybenzene, 45 ml of triethylamine, and 6.0g (0.05 mol) of silicontetrachloride. In a separate vessel, carbon dioxide gas was bubbledthrough 22.1g (0.1 mol) of commercial 3-(triethoxysilyl)propylaminedissolved in 20 ml of dry benzene for 10 minutes to form the carbamicacid salt.

The suspension of carbamate was then added dropwise to the reactionflask over the period of 1 hour with stirring at room temperature, andthe mixture was allowed to stir for an additional 30 minutes at ambienttemperature. The mixed amine hydrochlorides were then filtered off andwashed with 30 ml of benzene.

The filtrate and washings upon distillation produced 12g of3-(triethoxysilyl)propyl isocyanate, bp 75° C. at 0.05 torr, which was a97% yield.

EXAMPLE 7

This Example illustrates the synthesis of 1,6 hexamethylene diisocyanateby the exchange method.

Into a stirred 500 ml flask under nitrogen, there were charged, insequence, 11.6g (0.1 mol) of 1,6 hexamethylenediamine in 200 ml of dryTHF, 28 ml of triethylamine, and 24 ml (21.6g, 0.2 mol) oftrimethylchlorosilane. Carbon dioxide gas was lowly passed into thereaction mixture at reflux for 4 hours.

After stopping the carbon dioxide, 32 ml (42.2g., 0.2 mol) ofphenyltrichlorosilane was added; and the heating at reflux was continuedfor an additional 6 hours. After cooling to room temperature, thereaction mixture was filtered under nitrogen to remove the triethylaminehydrochloride.

The filtrate and washings yielded 13.5g of 1,6 hexamethylenediisocyanate, bp 78°-80° C. at 0.05 torr, an 80% yield.

EXAMPLE 8

This Example illustrates the synthesis of cyclohexyl isocyanate by theexchange method, described in Example 7.

Under nitrogen, 19.8g (0.2 mol) of cyclohexylamine was treated withcarbon dioxide gas for 5 minutes to form the carbamic acid salt. 200 mlof dry THF and 14 ml (0.12 mol) of trimethylchlorosilane were thenadded, and the mixture heated at reflux for 2 hours. The reactionmixture was then cooled, filtrated, and washed as described in Example7; and the filtrate and washings containing the silylcarbamate were putback into the original flask.

While the mixture was being stirred, 6 ml (0.05 ml) of silicontetrachloride was added at once by means of a syringe. A whiteprecipitate of trichlorosilylcarbamate formed; and the reaction mixturewas the heated at reflux for five hours. The infrared spectrum of themixture showed disappearance of the carbamate carbonyl band at 5.8μ andappearance of the isocyanate absorption band at 4.45μ.

The reaction mixture was then cooled, concentrated in a rotaryevaporator at about 12 torr, and distilled to give 11.8g of cyclohexylisocyanate, bp 167°-169° C., a 94% conversion.

EXAMPLE 9

This Example demonstrates the synthesis and isolation of the halosilylcarbamate intermediate.

By the method of Example 1, 13.4g of dimethylammonium dimethylcarbamatewas made from dimethylamine gas and Dry Ice in a nitrogen atmosphere.The carbamic acid salt was added to 100 ml of dry tetrahydrofuran; and,with stirring at room temperature, 12 ml (10.8g, 0.1 mol) oftrimethylchlorosilane was added at once with a syringe. The reactionmixture was than allowed to air for 16 hours.

From this reaction, 16.2 ml (21.1g, 0.1 mol) oftrimethylsilyl-N,N-dimethyl carbamate resulted, following removal ofdimethylamine hydrochloride by filtration. The filtrate was stirredfurther at room temperature, and 16.0 ml (0.1 mol) ofphenyltrichlorosilane was added to once with a syringe. The reactionmixture was allowed to stir for an additional 16 hours. Concentration ofthe reaction mixture with a rotary evaporator at 35°-40° C. at about 12torr yielded, quantitatively, 26g ofphenydichlorosilyl-N,N-dimethylcarbamate.

Infrared spectrometry showed disappearance of the alkyl-substitutedsilylester carbonyl absorption band at 5.92μ and the appearance of thearomatic-substituted silylester carbonyl band at 5.92μ. The nuclearmagnetic resonance (nmr) spectrum of this compound in CDCl₃ was recordedon a Varian A-60 spectrometer and showed signals at δ 2.83 (m,6,-NCH₃)and 7.55 ppm (m,5,aromatic protons).

EXAMPLE 10

The procedure of Example 9, in general, was followed to prepare, fromcyclohexylamine, the corresponding halosilylcarbamate.

The carbamic acid salt was first made from the amine and carbon dioxide,as illustrated in Example 8. The salt was then converted to asilylcarbamate by reaction with trimethylchlorosilane, as also describedin Example 8.

To 2.1g (0.01 mol) of trimethylsilyl-N-cyclohexylcarbamate dissolved in200 ml of tetrahydrofuran at room temperature, there was then added 1.6ml of phenyltrichlorosilane; and the mixture was allowed to stir for 16hours.

The solvent was then removed at 35°-40° C. in a rotary evaporator undervacuum, forming, in quantitative yield, 3.1g of white, crystallinephenyldichlorosilyl-N-cyclohexylcarbamate. This intermediate, whenheated, quickly decomposed to yield cyclohexyl isocyanate.

The intermediate was characterized in its infrared spectrum by a shiftin carbonyl absorptions from 5.90 to 5.79μ, showing replacement of analkyl-substituted silylester carbonyl by an aromatic-substitutedsilylester carbonyl. This halosilylcarbamate in deuteriochloroform gavean nmr spectrum with absorption bands at δ 1.6 (m, 10, --CH₂ --), 3.6(m,1, --CHN) and 7.5 ppm (m, 5, aromatic).

EXAMPLE 11

This Example illustrates the synthesis of an isocynate from an aminebearing a further reactive, functional group:2-(4'-hydroxyphenyl)ethylamine (trivially-tyramine).

Into a 250 ml, three-necked flask fitted with a reflux condenser, gasinlet tube and magnetic stirrer and kept under a positive pressure ofdry nitrogen, there was charged 100 ml of dry tetrahydrofuran, 1.4g(0.01 mol) of tyramine and 5.0 ml of triethylamine. 3.0 ml oftrimethylchlorosilane was then added at ambient temperature, dropwiseand with stirring over a period of 30 minutes. Carbon dioxide wasthereafter slowly bubbled into the reaction mixture, via a syringeneedle for 4 hours while the mixture was allowed to reflux for the sameperiod. Introduction of carbon dioxide was then terminated, and 1.5 mlof silicon tetrachloride was added slowly using a syringe. After 30minutes of additional heating, the reaction mixture was allowed to cool,and triethylamine hydrochloride was removed by filtration. The solventwas then removed at 35° C. in vacuo (12 torr), and the resulting oildistilled at 88°-90° C. (0.05 torr) to give2-(4'-trimethylsiloxyphenyl)ethyl isocyanate as a colorless liquid.

The infrared spectrum of this novel compound showed absorption bands at3.39, 4.41, 6.17 and 6.58μ. The nmr spectrum in CDCl₃ showed absorptionsat δ7.08 and 6.77 (A₂ B₂ q, 4, J = 8.4 Hz, aromatic 3'-, 5'- and 2'-,6'-protons, respectively), 3.43 (t, 2, J = 6.6 Hz, --CH₂ CH₂ --N), 2.79(t, 2, J = 6.6 Hz, --CH₂ CH₂ N) and 0.25 ppm (s, 9, --OSi(CH₃)₃). Themass spectrum showed a molecular ion at m/e 235, and additional peaks at179, 163, 107 and 73, and a metastable peak at 163.3.

EXAMPLE 12

This Example demonstrates the synthesis ofmethyl-2-isocyanato-3-(4'-trimethylsiloxyphenyl)propionate(trivially-blocked L-tyrosine methyl ester isocyanate).

Through a stirred mixture of 9.75g (0.05 mol) of L-tyrosine methylester, suspended in 200 ml of dry tetrahydrofuran and 45 ml (0.30 mol)of triethylamine, there was bubbled a stream of dry carbon dioxide.After 30 minutes, 20 ml (0.16 mol) of trimethylchlorosilane was addedslowly; and the mixture, with carbon dioxide continuously bubblingthrough, was allowed to reflux for 4 hours. The reaction mixture wasthen allowed to cool to room temperature, the carbon dioxide bubblingdiscontinued, 8.5g (6.0 ml, 10.05 mol) of silicon tetrachloride slowlyadded, and the mixture allowed to stir at ambient temperature for 20minutes.

The mixture was thereafter allowed to reflux for one hour, then cooledto ambient temperature, and 50 ml of tert-butyl alcohol was added. Themixture was then allowed to stir at ambient temperature for 30 minutes.The mixture was then filtered under nitrogen, the filter cake washedwith 30 ml of dry THF, and the combined filtrates concentrated in vacuoand distilled using a short-path column.

The fraction collected at 100°-145° C. (0.05 mm) was redistilled to give5.8g (39%) of methyl-2-isocyanato-3 (4'-trimethylsiloxyphenyl)propionateas a viscous, colorless oil: bp 139°-40° C. (0.1 mm); ir (neat smear)3.38, 4.45 (N═C═O), 5.73 (ester C═O), 6.22, 6.64, 10.9 and 11.8μ; nmr(CCl₄) δ 7.00 and 6.70 (A₂ B₂ q, 4, J = 8.6 Hz, aromatic 3'-, 5'- and2'-, 6'-protons, respectively), 4.10 (t, 1, J = 6.0 Hz, --CH₂ --CH--),3.66 (s, 3, --OCH₃), 2.91 (d, 2, J = 6.0 Hz, --CH₂ --CH--) and 0.22 ppm(s, 9, (CH₃)₃ Si--); mass spectrum (70eV) m/e (rel intensity) 293 (5),278 (1.5), 250 (1), 234 (2.5), 218 (0.75), 179 (100), 163 (2.3), 149(2), 107 (2), and 73 (40).

EXAMPLE 13

This Example illustrates the synthesis ofmethyl-2-isocyanato-3-(4'-tert-butyldimethylsiloxyphenyl) propionate.

The procedure of Examples 12 and 13 was, in general, followed. Into 100ml of dry tetrahydrofuran there was added 8.0g (0.04 mol) of L-tyrosinemethyl ester. A slow stream of dry carbon dioxide gas was bubbled intothe stirred reaction mixture for 30 minutes while 50 ml of triethylaminewas added dropwise. 15g (0.1 mol) of tert-butyldimethylchlorosilane wasthen added, and the reaction mixture was heated at reflux for 4 hours.After cooling, 8.5g (6.0 ml, 0.05 mol) of silicon tetrachloride wasadded, whereupon the reaction mixture was stirred for 30 minutes andheated at reflux for 1 additional hour. 50 ml of tert-butyl alcohol wasthen added to decompose any silylchlorides and stirring was continuedfor an additional 30 minutes.

After filtration, washing, and concentration of the reaction mixture asdescribed in the prior Examples, 2.7g (20 percent yield) of colorlessisocyanate boiling at 180° C. (0.5 torr) was isolated. Infraredabsorption peaks (smear) were found at 3.38, 4.44, 5.71, 6.17 and 6.54μ.The nmr spectrum (CDCl₃) was characterized by signals at δ 7.83 and 6.83(A₂ B₂ q, 4 J = 8.6 Hz, aromatic 3'-, 5'- and 2'-, 6'-protons,respectively), 4.26 (t, 1, J = 6.0 Hz, --CH₂ CH), 3.83 (s, 3, --OCH₃),3.08 (d, 2, J = 6.0 Hz, --CH₂ CH--), 1.03 (s, 9, --C(CH₃)₃) and 0.26 ppm(s, 6, --Si(CH₃)₂). The mass spectrum showed peaks at m/e 335, 278, 250,236, 221, 205, 172, 73 and 57.

EXAMPLE 14

This Example illustrates the synthesis of 2-trimethylsiloxyethylisocyanate by the exchange method described in Example 7.

Under nitrogen, 6.1g (0.1 mol) of ethanolamine and 100 ml oftriethylamine dissolved in 100 ml of dry THF was treated with carbondioxide gas to form the carbamic acid salt. 24 ml (0.2 mol) oftrimethylchlorosilane was then added with a syringe and the mixtureheated at reflux for 2 hours. At this point, the carbon dioxide gastreatment was discontinued and the reaction mixture was then cooled,filtered and washed as described in Example 7; and the filtrate andwashings containing the silylcarbamate were put back into the originalflask.

While the mixture was being stirred, 12 ml (0.05 mol) of silicontetrachloride was added dropwise over a period of 15 minutes. Thereaction mixture was then allowed to stir overnight, filtered,concentrated under vacuum and distilled to give 2-trimethylsiloxyethylisocyanate, bp 27'-29° C. at 0.02 millimeters.

The ir (neat smear) showed 3.42, 4.42 (N═C═C), 8.0 (TMS), 9.0, 10.67 and11.95μ. The nmr spectrum in CDCl₃ showed absorptions at δ 3.71 (t, 2, J= 5.0 Hz), 3.28 (t, 2, J = 5.0 Hz), and 0.16 ppm (s, 9, Si--(CH₃)₃.

What is claimed is:
 1. A process of preparing isocyanates in a liquidphase reaction from primary amines which comprises reacting a primaryamine with carbon dioxide to form the corresponding carbamic acid salt,reacting the carbamic acid salt to form a halosilyl carbamate having theformula:

    RNHCOOSiXY.sub.2

wherin R is the organic moiety of the primary amine, X is halogen and Yis a member selected from the group consisting of halogen, hydrogen,lower alkyl, alicyclics, aryl, alkaryl and aralkyl, each having no morethan about 10 carbon atoms, and heating the halosilyl carbamate to atemperature and for a time sufficient to yield the isocyanate.
 2. Theprocess of claim 1 wherein the halosilyl carbamate is formed from thecarbamic acid salt by reacting the carbamic acid salt with a halosilanehaving the formula:

    SiX.sub.2 Y.sub.2

wherein X is halogen and Y is a member selected from the groupconsisting of halogen, hydrogen, lower alkyl, alicyclics, aryl, alkaryland aralkyl, each having no more than about 10 carbon atoms.
 3. Theprocess of claim 1 wherein the halosilyl carbamate is formed from thecarbamic acid salt by reacting the carbamic acid salt with amonohalosilane to form the silyl carbamate and then trans-silylating thesilyl carbamate by reaction with a halosilane having the formula:

    SiX.sub.2 Y.sub.2

wherein X is halogen and Y is a member selected from the groupconsisting of halogen, hydrogen, lower alkyl, alicyclics, aryl, alkaryl,and aralkyl, each having no more than about 10 carbon atoms.
 4. Theprocess of claim 1 wherein the process is carried out at a temperaturein the range of from ambient to about 150° C.
 5. The process of claim 1wherein the process is carried out at a temperature in the range of fromabout 30° C. to about 60° C.
 6. The process of claim 1 wherein theprocess is carried out in the presence of a tertiary amine as a solvent.7. The process of claim 6 wherein the tertiary amine is triethylamine.8. The process of claim 2 wherein the halosilane is a chlorosilane. 9.The process of claim 2 wherein the halosilane is a member selected fromthe group consisting of silicon tetrachloride, phenyltrichlorosilane anddimethyldichlorosilane.
 10. The process of claim 2 wherein thehalosilane is silicon tetrachloride.
 11. The process of claim 3 whereinthe halosilane is a chlorosilane.
 12. The process of claim 3 wherein thehalosilane is a member selected from the group consisting of silicontetrachloride, phenyltrichlorosilane and dimethyldichlorosilane.
 13. Theprocess of claim 3 wherein the halosilane is silicon tetrachloride. 14.The process of claim 1 wherein the organic radical of the primary aminecontains at least one reactive, functional group.